Various publications, including patents, published applications, technical articles and scholarly articles are cited throughout the specification. Each of these cited publications is incorporated by reference herein, in its entirety.
Exposure to certain metals and metalloids has been implicated in various ill effects on human and animal health. Such metals are often referred to as heavy metals or toxic metals, although these terms are often used inconsistently, and there is no standard or even consensus as to what characteristics classifies a metal as heavy or toxic. Nevertheless, even low levels of exposure to some of these metals has been associated with neurotoxicity, nephrotoxicity, teratogenicity, cancer, and the like.
Heavy metals are prevalent in all environments, and are present there both naturally and through human activity such as pollution. Exposure to such metals can be by way of ingestion of contaminated food or water, inhalation of contaminated air, by absorption through the skin or mucosal membranes, and the like. In many cases, even low level exposure can result in adverse health effects.
One particular metal, lead, remains a worldwide health concern, especially in children. There is increasing recognition that there is no safe level of lead exposure. Lead exposure is problematic for children because lead can accumulate in their nervous system, and can also readily cross their blood brain barrier, which is not fully developed. Stricter environmental regulation, particularly in developed countries, has significantly reduced lead exposure in children, although remnants of a bygone era such as lead-based paint, and lead-based plumbing, still prevalent in older and urban homes and businesses, are cause for many cases of lead-poisoning in the United States alone.
In developing nations, lead exposure and poisoning is a prevalent problem. This is because such nations, often having lax or non-existent environmental regulations, permit the continued sale and use of gasoline containing lead additives, lead-based paint, lead-based cosmetics such as lead-kohl, lead-plumbing, and lead-solder. Parts of South America, Sub-Saharan Africa, Asia, Eastern Europe, and the Middle East have persistent problems with lead-contamination of the environment.
The adverse effects of lead exposure are often not immediately apparent. Prolonged exposure, however, generally manifests itself in children by irritability, a loss of appetite and weight, pain, anemia, learning difficulty and disabilities, stunted growth, impaired hearing and low IQ, among other things. In adults, lead poisoning can manifest itself through pain and numbness in extremities, headaches, memory loss, mood disorders, and reduced sperm count. Rates of childhood lead exposure have also been linked to the rate of violent crime.
Many of the effects of lead exposure can be reversed with proper treatment, although many other effects, particularly the neurological effects, are irreversible. In general, more intense therapies are indicated for higher levels of exposure. A proper treatment regimen for lead exposure, however, depends on a proper diagnosis.
At the present time, lead exposure, including the level or extent of exposure, is usually diagnosed by assaying for the amount of lead in the blood. The invasive aspect of blood testing carries with it a general reluctance or unwillingness for people to get needed testing, which may in turn delay treatment, and they may thus risk irreversible damage. In addition, blood testing can be particularly traumatic for younger children, who are the most at risk for adverse health effects of lead exposure. Less invasive screening methods, then, are desired in order to secure greater compliance with lead testing protocols.
Common non-invasive screens for various diagnostics include the collection and analysis of other bodily fluids such as urine, saliva, and sputum. Avoiding blood analysis provides the additional advantage of increased safety for the investigator. With respect to diagnosis of toxic metal exposure, and more particularly with respect to diagnosis of lead exposure, such non-invasive screens have not met with success. Urinalysis, fecal analysis, hair analysis, and nail analysis, suffer from various shortfalls (Barbosa F et al. (2005) Environ. Health Perspect. 113:1669-74). With respect to saliva, variation in saliva production, saliva stimulation, lack of proper standards, absence of reliable reference values for human populations, and low levels of lead actually present in the saliva limit the utility of saliva in a determination of lead exposure. Indeed, several investigators have concluded that salivary lead is not suitable for determining lead exposure (see, e.g., Barbosa F et al. (2006) Arch. Toxicol. 80:633-7; Thaweboon S et al. (2005) Southeast Asian J. Trop. Med. Public Health. 36:1576-9; and, Koh D et al. (2003) Occup. Environ Med. 60:696-8). Some recent data, however, suggests a weak association between blood lead and saliva lead concentrations (Nriagu J et al. (2006) Int. J. Hyg. Environ. Health. 209:109-121). Nevertheless, to date, blood analysis remains the gold standard for proper detection and diagnosis of lead exposure and poisoning.